Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

Abstract

AbstractPyridines and quinolines substituted with sulfur‐containing functional groups are widely used as drugs, drug candidates, organic materials, N,S‐ligands and others. Traditional synthetic routes to produce these compounds are based on nucleophilic aromatic substitution reactions and transition metal‐catalyzed cross‐coupling reactions of (pseudo)halopyridines. While effective in many cases, both approaches are limited due to using forcing conditions and expensive, specifically designed catalytic systems. In the last decade, a number of innovative methods for the functionalization of the pyridine ring via the formation of a C−S bond have been developed. Most of these methods proceed through the direct or indirect C−H functionalization of unfunctionalized pyridines, thus avoiding the use of oftentimes not readily available halopyridines as the starting materials. Deoxygenative C−H functionalization of pyridine‐N‐oxides and deaminative transformation of aminopyridines have been also employed for the introduction of diverse organosulfur functionality into the pyridine ring. All these processes can be easily performed under mild conditions, typically affording value pyridines and quinolines in good to high yields. Usually being highly chemo‐ and regioselective, these methods allow the late‐stage functionalization of complex molecules including drugs and natural products. In this Review, we summarize the most recent synthetic methods for functionalization of pyridines and fused pyridines with sulfur‐containing functional groups reported mostly since 2018. For a better understanding of the processes, the mechanisms of the described reactions are briefly discussed.